This invention relates to 1,4,7,10-tetraazacyclodedecane butyltriols, their complexes and complex salts, agents containing these compounds, their use as diagnostic agents and therapeutic agents as well as processes for the production of these compounds and agents.
In European patent application 87730085.5 with the publication number 0 255 471 macrocyclic compounds of general formula I are claimed,in which
Y is a nitrogen atom or phosphorus atom,
A1 and A2 are the same or different and each is a straight-chain or branched alkylene group with 2 to 6 carbon atoms,
U1, U2, U3, U4 are the same or different and each is a direct bond or a straight-chain or branched alkylene group with 1 to 6 carbon atoms,
D1, D2, D3, D4 are the same or different and each is an oxygen atom or sulfur atom, an alkylene group with 1 to 6 carbon atoms or a group N-R7 with R7 meaning a hydrogen atom, a straight-chain or branched alkylene chain with 1 to 4 carbon atoms, which on the end carries a COOR1 group, and R1 stands for a hydrogen atom or a metal ion equivalent.
D5 has the meaning indicated for D1, D2, D3 and D4 aswell as the group with R5 meaning a hydrogen atom or a straight-chain or branched saturated or unsaturated C1-C20 alkylene group, optionally substituted by hydroxy, mercapto, imino and/or amino group(s), optionally containing imino, phenylenoxy, phenylenimino, amide, ester group(s), oxygen atom(s), sulfur atom(s) and/or nitrogen atom(s), which on the end exhibits either a functional group or a macromolecule B bound by it,
s and t represent whole numbers from 0 to 5,
R2 represents hydrogen, a straight or branched, saturated or unsaturated alkyl, acyl or acylalkyl group with 1 to 16 carbon atoms optionally substituted by one or more hydroxy or lower alkoxy groups,
—CH2—X—V with X meaning carbonyl, a straight-chain or branched-chain alkylene group with 0 to 10 carbon atoms, which optionally is substituted by one or more hydroxy or lower alkoxy groups or a straight-chain or branched-chain alkylene group interrupted by oxygen atoms with 2 to 23 hydrocarbon atoms,
V meaning of —COOR6, and R3 and R4, independently of one another, represent hydrogen, a straight or branched alkyl group with 1 to 16 carbon atoms optionally substituted by one or more hydroxy or lower alkoxy groups or R3 and R4 together with the nitrogen atom represent a saturated five or six ring optionally containing another heteroatom and R6 represents hydrogen or a saturated, unsaturated straight-chain or branched-chain or cyclic hydrocarbon radical with up to 16 carbon atoms or an aryl or aralkyl group,
or
R2 or R3 represent a second macrocycle of formula I′—bound by an alkylene chain (K) containing 2 to 20 carbon atoms, which optionally carries carbonyl groups on the ends and optionally is interrupted by one or more oxygen atoms or R1 carboxymethylimino groups or is substituted by one or more hydroxy, lower alkoxy or carboxy lower alkyl groups—which can be of a different structure than the parent substance of the first, or
R2 means B or CH2—COB,
provided that, if R2 stands for B or CH2—COB, R5 means a hydrogen atom, that at least two COOR1 groups are present in the molecule and that two heteroatoms of the macrocycle are each connected by an alkylene group with at least two carbon atoms, and functional groups existing in the molecule optionally are conjugated with macromolecules and optionally free carboxyl groups are made into salts with organic or inorganic bases or amino acids and basic groups with inorganic or organic acids.
The substances and the solutions prepared from them meet the demands to be made of pharmaceutically usable chelates. They have a strong and adaptable effectiveness, by the selection of suitable metal atoms, on the respective principles of the diagnostic or therapeutic method (x ray, NMR, ultrasound, nuclear medicine).